Dinitrophenol toxicity: Difference between revisions

Latest revision as of 17:13, 18 May 2020

Background

Used in the manufacture of munitions, as a dye, a wood preserver, herbicide and photograph developer
- Can lead to unintentional exposures
Discovered as a weight loss drug in 1930's but banned by FDA soon afterwards due to side effects
Now banned in US and UK as weight loss drug, labeled "not fit for human consumption"
Able to purchase DNP online in mass quantities^[1]
- Typically used by body builders for weight loss
- Suicidal intentional ingestion
- Increase in number of deaths in recent years
Case reports indicate that 20–50mg per kilogram of body weight in humans can be lethal^[2]

Pharmacology

Uncouples oxidative phosphorylation
- Allows increase in basal leak of protons (H+) accross the mitochondrial membrane which is dissipated as heat and leads to hyperthermia
Stimulation of glycolysis in small doses

Clinical Features

Very narrow therapeutic window

"Theraputic dose"

Pruritic rash
Yellow discoloration of skin, eyes, and urine (appears similar to jaundice)
Peripheral neuropathy
anorexia
confusion
cataracts
deafness
coma

Acute toxicity

Profuse diaphoresis
Hyperthermia
Tachypnia
Tachycardia
Irregular pulse
Agitation
Headaches
Dizziness
Blurry vision
Confusion
Restlessness
Dehydration
Thirst
Flushed skin
Cyanosis
Abdominal pain
Nausea
Vomiting
Diarrhea
Muscular spasms
Mayalgia
Pulmonary edema
Trismus
Cytotoxic cerebral edema
Acute congestion of the liver
Convulsions
Coma
Shock/cardiovascular collapse
PEA/death

Differential Diagnosis

Fever

Infectious

Critical
- Sepsis
- PNA with respiratory failure
- Peritonitis
- Meningitis
- Cavernous Sinus Thrombosis
- Necrotizing Fasciitis
Emergent
- PNA
- Peritonsillar Abscess
- Retropharyngeal Abscess
- Epiglottitis
- Endocarditis
- Pericarditis
- Appendicitis
- Cholecystitis
- Diverticulitis
- Intra-abdominal abscess
- Pyelonephritis
- Tubo-ovarian abscess
- Encephalitis
- Brain abscess
- Cellulitis
- Abscess
- Malaria
Non-emergent
- Viral syndrome
- Otitis Media
- Sinusitis
- Pharyngitis
- Influenza
- TB
- UTI
- Epididymitis
- Prostatitis

Non-infectious

Critical
Emergent
- CHF
- Dehydration
- Recent Seizure
- Sickle Cell Dz
- Transplant rejection
- Pancreatitis
- DVT
- Serotonin Syndrome
Non-emergent
- Drug fever (except as in NMS and Serotonin Syndrome)
- Malignancy
- Gout
- Sarcoidosis
- Crohn's Disease
- Postmyocardiotomy syndrome
- Sweet's syndrome

Toxicologic causes of Hyperthermia

Endocrine causes of Hyperthermia

Neurologic causes of Hyperthermia

Evaluation

High clinical suspicion needed"

Blood glucose
CBC
Chemistry
Arterial blood gas or Venous blood gas
- Co-oximetry to evaluate for methemoglobinemia
Lactate
Coagulation studies
Creatine phosphokinase
Urine analysis
ECG
Chest x-ray
CT brain and/orLP as needed

Management

Decontamination with removal of clothing and irrigation as needed
Constant body temperature monitoring, cardiac monitor, IV access, and code cart to bedside
Activated charcoal if within 1 hour of ingestion
- No evidence for or against multiple doses of charcoal or whole bowel irrigation
Aggressive IVF administration (cooled if possible)
Vasopressors with cardiovascular collapse non-responsive to IVF
Treat methemoglobinemia as needed

Hyperthermia

External cooling with blankets, ice, and cooling devices
Cool IVF
Control agitation (adds to hyperthermia)

Agitation

Benzodiazepines should be administered as needed
- Paralyze and intubate if not controlled, but maintain continuous and aggressive sedation
Dantrolene has been used to manage DNP hyperthermia^[3]

Disposition

Admission for most patients
Observation if stable

External Links

References

↑ Grundlingh, Johann, Paul I. Dargan, Marwa El-Zanfaly, and David M. Wood. "2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death." Journal of Medical Toxicology J. Med. Toxicol. 7.3 (2011): 205-12. Web.
↑ Hsiao AL et al. "Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement"". Clin Toxicol (Phila). 2005. 43(4): 281–285.
↑ Kumar S, Barker K, Seger D. Dinitrophenol-induced hyperthermia resolving with dantrolene administration. Clin Toxicol. 2002;40:599-673.

Authors:

[1] Grundlingh, Johann, Paul I. Dargan, Marwa El-Zanfaly, and David M. Wood. "2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death." Journal of Medical Toxicology J. Med. Toxicol. 7.3 (2011): 205-12. Web.

[2] Hsiao AL et al. "Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement"". Clin Toxicol (Phila). 2005. 43(4): 281–285.

[3] Kumar S, Barker K, Seger D. Dinitrophenol-induced hyperthermia resolving with dantrolene administration. Clin Toxicol. 2002;40:599-673.

[1]

[2]

[3]

@@ Line 8: / Line 8: @@
 **Suicidal intentional ingestion
 **Increase in number of deaths in recent years
+*Case reports indicate that 20–50mg per kilogram of body weight in humans can be lethal<ref>Hsiao AL et al. "Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement"". Clin Toxicol (Phila). 2005. 43(4): 281–285.</ref>
 ===Pharmacology===
@@ Line 16: / Line 17: @@
 ==Clinical Features==
 ''Very narrow therapeutic window''
-;"Theraputic dose"
+==="Theraputic dose"===
 *Pruritic rash
 *Yellow discoloration of skin, eyes, and urine (appears similar to [[jaundice]])
@@ Line 25: / Line 26: @@
 *deafness
 *coma
-;acute toxicity
-*profuse diaphoresis
+===Acute toxicity===
-*hyperthermia
+*Profuse diaphoresis
-*tachypnia
+*Hyperthermia
-*tachycardia
+*Tachypnia
-*convulsions
+*Tachycardia
-*shock/cardiovascular collapse
+*Irregular pulse
+*Agitation
+*Headaches
+*Dizziness
+*Blurry vision
+*Confusion
+*Restlessness
+*Dehydration
+*Thirst
+*Flushed skin
+*Cyanosis
+*Abdominal pain
+*Nausea
+*Vomiting
+*Diarrhea
+*Muscular spasms
+*Mayalgia
+*Pulmonary edema
+*Trismus
+*Cytotoxic cerebral edema
+*Acute congestion of the liver
+*Convulsions
+*Coma
+*Shock/cardiovascular collapse
 *PEA/death
 ==Differential Diagnosis==
-*[[jaundice]]
+{{Differential diagnosis hyperthermia}}
-*{{Acute fever DDX}}
-==Diagnosis==
+==Evaluation==
+''High clinical suspicion needed"
+*Blood glucose
+*CBC
+*Chemistry
+*Arterial blood gas or Venous blood gas
+**Co-oximetry to evaluate for [[methemoglobinemia]]
+*[[Lactate]]
+*Coagulation studies
+*Creatine phosphokinase
+*[[Urine analysis]]
+*[[ECG]]
+*[[Chest x-ray]]
+*[[CT brain]] and/or[[LP]] as needed
 ==Management==
+*Decontamination with removal of clothing and irrigation as needed
+*Constant body temperature monitoring, cardiac monitor, IV access, and code cart to bedside
+*[[Activated charcoal]] if within 1 hour of ingestion
+**No evidence for or against multiple doses of charcoal or whole bowel irrigation
+*Aggressive [[IVF]] administration (cooled if possible)
+*Vasopressors with cardiovascular collapse non-responsive to IVF
+*Treat [[methemoglobinemia]] as needed
+===[[Hyperthermia]]===
+*External cooling with blankets, ice, and cooling devices
+*Cool IVF
+*Control agitation (adds to hyperthermia)
+===Agitation===
+*[[Benzodiazepines]] should be administered as needed
+**Paralyze and intubate if not controlled, but maintain continuous and aggressive sedation
+*[[Dantrolene]] has been used to manage DNP hyperthermia<ref>Kumar S, Barker K, Seger D. Dinitrophenol-induced hyperthermia resolving with dantrolene administration. Clin Toxicol. 2002;40:599-673.</ref>
 ==Disposition==
+*Admission for most patients
+*Observation if stable
 ==See Also==
+*[[Hyperthermia]]
+*[[Clenbuterol toxicity]]
 ==External Links==
+*[https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAttachment.aspx?Attachment_id=103205 Public Health England - DNP (2,4 dinitrophenol) toxicity]
+*[https://www.atsdr.cdc.gov/ToxProfiles/tp64.pdf DHHS - Toxicological Profile for Dinitrophenols]
+*[https://aapcc.org/annual-reports AAPCC - National Poison Data System Annual Reports]
 ==References==
-<references/>
+[[Category:Toxicology]]